Possibilities of microemulsion application in rectal administration of indomethacin

Abstract

Abstract Rectal administration is a suitable route of administration for drugs that are either very irritating to the intestine (e.g., indomethacin) or are more effective when the first-pass effect in the liver is circumvented. Microemulsions are a tool for the improvement of penetration of sparingly soluble drugs. They are mainly used in topical and transdermal drug delivery. However, they find application also in other routes of administration, mainly due to their ability to solubilize sparingly soluble drugs. The selection of a suppository base depends on the physical properties of the drug. The study focused on evaluating the effect of the microemulsion as the solubilizer of sparingly soluble indomethacin in hydrophilic and lipophilic suppository bases compared with Polysorbate 80 as the excipient contained in the microemulsion. The reference suppositories were prepared by the traditional moulding technique from Adeps solidus or Macrogol suppository base without the previous drug solubilization. The microemulsion-based suppositories were prepared after the initial solubilization of the drug in the microemulsion or Polysorbate 80, followed by the addition of suppository base to maintain the same drug/solubilizer ratio. The suppositories were tested for softening time, hardness, and uniformity of mass. The dissolution test was performed using the dialysis tubing method in the basket apparatus. The amount of indomethacin released into the dissolution medium was determined spectrophotometrically at 320 nm. The results indicate that solubilization of indomethacin in the microemulsion had a positive effect on in vitro drug release but not as significant as in the case of Polysorbate 80 used alone. The enhancement ratio for Polysorbate 80 in Adeps suppositories was 2.9, for the microemulsion in Adeps suppositories was 1.1, and for Polysorbate 80 in Macrogol suppositories was 7.4 after 3 hours. The test of uniformity of mass had shown that all suppositories (reference, solubilizer-containing) are within the permitted limits. The softening time was reduced by adding the solubilizer to each type of suppository base.